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oai:repisalud.isciii.es:20.500.12105/72372024-11-29T20:06:56Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Marión, Rosa M author Lopez de Silanes, Isabel author Mosteiro, Lluc author Gamache, Benjamin author Abad, María author Guerra Carmen, Carmen author Megias Vazquez, Diego author Serrano Marugan, Manuel author Blasco , MA author 2017-02-14 Reprogramming of differentiated cells into induced pluripotent stem cells has been recently achieved in vivo in mice. Telomeres are essential for chromosomal stability and determine organismal life span as well as cancer growth. Here, we study whether tissue dedifferentiation induced by in vivo reprogramming involves changes at telomeres. We find telomerase-dependent telomere elongation in the reprogrammed areas. Notably, we found highly upregulated expression of the TRF1 telomere protein in the reprogrammed areas, which was independent of telomere length. Moreover, TRF1 inhibition reduced in vivo reprogramming efficiency. Importantly, we extend the finding of TRF1 upregulation to pathological tissue dedifferentiation associated with neoplasias, in particular during pancreatic acinar-to-ductal metaplasia, a process that involves transdifferentiation of adult acinar cells into ductal-like cells due to K-Ras oncogene expression. These findings place telomeres as important players in cellular plasticity both during in vivo reprogramming and in pathological conditions associated with increased plasticity, such as cancer. Stem Cell Reports. 2017;8(2):460-475. 10.1016/j.stemcr.2017.01.001 2213-6711 22136711 Stem cell reports 28162998 http://hdl.handle.net/20.500.12105/7237 ADM TRF1 Cancer Cellular plasticity In vivo reprogramming Regeneration Stem cells Telomeres Transdifferentiation tumorigenesis Common Telomere Changes during In Vivo Reprogramming and Early Stages of Tumorigenesis